A novel social proximity test suggests patterns of social avoidance and gaze aversion-like behavior in BTBR T+ tf/J mice
Open accessAbstract
The BTBR T+ tf/J (BTBR) inbred mouse strain displays a low sociability phenotype relevant to the first diagnostic symptom of autism, deficits in reciprocal social interactions. Previous studies have shown that BTBR mice exhibit reduced social approach, juvenile play, and interactive behaviors. The present study evaluated the behavior of the BTBR and C57BL/6J (B6) strains in social proximity. Subjects were closely confined and tested in four experimental conditions: same strain male pairs (Experiment 1); different strain male pairs (Experiment 2); same strain male pairs and female pairs (Experiment 3); same strain male pairs treated with an anxiolytic (Experiment 4). Results showed that BTBR mice displayed decreased nose tip-to-nose tip, nose-to-head and upright behaviors and increased nose-to-anogenital, crawl under and crawl over behaviors. These results demonstrated avoidance of reciprocal frontal orientations in the BTBR, providing a parallel to gaze aversion, a fundamental predictor of autism. For comparative purposes, Experiment 3 assessed male and female mice in a three-chamber social approach test and in the social proximity test. Results from the three-chamber test showed that male B6 and female BTBR displayed a preference for the sex and strain matched conspecific stimulus, while female B6 and male BTBR did not. Although there was no significant interaction between sex and strain in the social proximity test, a significant main effect of sex indicated that female mice displayed higher levels of nose tip-to-nose tip contacts and lower levels of anogenital investigation (nose-to-anogenital) in comparison to male mice, all together suggesting different motivations for sociability in males and females. Systemic administration of the anxiolytic, diazepam, decreased the frequency of two behaviors associated with anxiety and defensiveness, upright and jump escape, as well as crawl under behavior. This result suggests that crawl under behavior, observed at high levels in BTBR mice, is elicited by the aversiveness of social proximity, and possibly serves to avoid reciprocal frontal orientations with other mice.
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BTBR T+tf/J mice display behavioral phenotypes relevant to all three diagnostic symptoms of autism.
“BTBR T+tf/J (BTBR) is a commercially available inbred strain of mouse that displays behavioral phenotypes relevant to all three diagnostic symptoms of autism (60–62, 64, 66, 68–70, 72, 74–78).”
From Negative allosteric modulation of the mGluR5 receptor reduces repetitive behaviors and rescues social deficits in mouse models of autism (2012) · cites this paper as [68]
Several naturally occurring inbred strains of mice display behavioral features that recapitulate diagnostic symptoms of neurodevelopmental disorders.
“Several naturally occurring inbred strains of mice display behavioral features that recapitulate diagnostic symptoms of neurodevelopmental disorders (59–70).”
From Negative allosteric modulation of the mGluR5 receptor reduces repetitive behaviors and rescues social deficits in mouse models of autism (2012) · cites this paper as [68]
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- Authors
- Defensor, E. B., Pearson, B. L., Pobbe, R. L. H., Bolivar, V. J., Blanchard, D. C., & Blanchard, R. J.
- Affiliations
- University of Hawaiʻi at Mānoa (US)
- New York State Department of Health (US)
- Corresponding author
- Defensor, Erwin B.
- Venue
- Behavioural Brain Research
- Publisher
- Elsevier BV
- Published
- 2011-03
- Volume
- 217
- Issue
- 2
- Pages
- 302-308
- ISSN
- 0166-4328 (ISSN-L)
- PMC
- PMC3124342
- OpenAlex
- W1992887691
- Cited by
- 136
- References
- 72
- Citations by year
- 2026: 3 · 2025: 5 · 2024: 3 · 2023: 9 · 2022: 10 · 2021: 8 · 2020: 10 · 2019: 9 · 2018: 9 · 2017: 3 · 2016: 9 · 2015: 11 · 2014: 13 · 2013: 5 · 2012: 19
- FWCI
- 6.59
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Behavioural Brain Research (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institute of Mental Health (MH081845-01A2)
- Topics
- Life Sciences › Neuroscience › Cognitive Neuroscience › Autism Spectrum Disorder Research
- Social Sciences › Psychology › Social Psychology › Neuroendocrine regulation and behavior
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetics and Neurodevelopmental Disorders
- Keywords
- BTBR T+tf/J mice, gaze aversion, social avoidance, autism model, sociability, reciprocal social interaction, diazepam, anxiolytic effects, C57BL/6J mice
- MeSH terms
- Analysis of Variance, Animals, Anxiety, Autistic Disorder, Behavior, Animal, Diazepam, Disease Models, Animal, Escape Reaction, Exploratory Behavior, Female, Male, Mice, Inbred C57BL, Sex Factors, Social Behavior, Anti-Anxiety Agents, Mice
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